1H MRSI/Response Inhibition/Methamphetamine Abusers

描述（由申请人提供）：项目摘要：与NIDA利用科学了解药物滥用和成瘾的使命一致，本提案服务于慢性甲基苯丙胺滥用的结构和功能神经病理学定位和特征的长期目标，慢性甲基苯丙胺滥用是一种具有重大公共卫生重要性的普遍情况。该项目的重点是减少对甲基苯丙胺滥用的反应抑制能力。反应抑制受损可能是额纹状体功能障碍的一种表现，被认为会使成瘾持续存在并影响治疗结果。具体来说，该项目将研究与反应抑制和/或受甲基苯丙胺滥用影响的大脑区域的代谢。神经代谢将用质子磁共振光谱成像（1H MRSI）进行检测，这是一种相对较少使用的技术。甲基苯丙胺滥用者将在短暂戒断后进入治疗前接受无创体内1H核磁共振成像扫描，并与年龄和性别匹配的健康对照进行比较。研究终点将包括代谢物A/-乙酰基化合物、谷氨酸；+谷氨酰胺+ GABA，肌酸+磷酸肌酸，胆碱化合物和肌醇在额叶下皮层，前扣带皮层，前扣带白质和伏隔核。我们将在短时间内获得1H磁共振成像，使我们能够以更高的空间分辨率从更多的大脑结构中取样更多的神经代谢物，而不是之前的研究。这提高了检测任何可能与甲基苯丙胺滥用有关的代谢物异常的可能性，并使它们能够在大脑结构和组织类型方面更精确地定位。因此，我们将在进入治疗时捕获甲基苯丙胺成瘾者大脑的广泛代谢概况。的相关性。非法甲基苯丙胺滥用是美国乃至世界范围内普遍存在的严重公共卫生问题。对许多人来说，甲基苯丙胺成瘾如此难以克服的一个可能原因是，上瘾者抑制自己寻求毒品的能力被认为受到脑损伤的损害。该项目将检查被认为对甲基苯丙胺成瘾者的抑制和/或损伤负责的大脑部分的化学成分。

DESCRIPTION (provided by applicant): Project Summary: Consistent with the NIDA mission of using science to understand drug abuse and addiction, this proposal serves the long-term objective of localizing and characterizing structural and functional neuropathology in chronic methamphetamine abuse, a widespread condition of major public health importance. The project focuses on diminished capacity for response inhibition in methamphetamine abuse. Impaired response inhibition is a likely manifestation of frontostriatal dysfunction and is believed to perpetuate addiction and to compromise treatment outcome. Specifically, this project will investigate the metabolism of brain regions involved with response inhibition and/or afflicted by methamphetamine abuse. Neurometabolism will be assayed with proton magnetic resonance spectroscopic imaging (1H MRSI), a comparatively underused technology in this condition. Methamphetamine abusers will undergo non-invasive, in vivo 1H MRSI scans just before entering treatment after brief abstinence and will be compared to age- and sex-matched healthy controls. Study endpoints will include levels of the metabolites A/-acetyl compounds, glutamate;+ glutamine + GABA, creatine +'phosphocreatine, choline compounds, and myo-inositol in inferior frontal cortex, anterior cingulate cortex, anterior cingulate white matter, and nucleus accumbens. We will acquire 1H MRSI at shot echo-time permitting us to sample a greater number of neurometabolites from more brain strucures at higher spatial resolution than reported in previous studies. This raises the probability of detecting any metabolite abnormalities that mayattend methamphetamine abuse and allows them to be localized with greater precision in terms of brain structure and tissue type. We will thus capture a wide metabolic profile of the methamphetamine addict's brain at time of entry into treatment. Relevance. Abuse of illicit methamphetamines is a serious public health problem of epidemic proportion in the US and abroad. One (1) possible reason methampetamine addiction is so difficult for many to overcome is that the addict's ability to inhibit him-or herself in seeking drug is thought to be compromised by brain damage. This project will examine the chemistry of parts of the brain thought to be responsible for inhibition and/or damaged by methamphetamine in methamphetamine addicts.